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Abstract: 5358

A25 - Mechanisms of immune dysfunction 13 A25
PD-1 serves as a marker of cytotoxic dysfunction in HIV+ individuals with controlled viral loads
but not in HIV+ individuals with higher viral loads and a more marked immunodeficiency

M.C. Iglesias Chiesa, N.G. Hernández Alvarez, A. Cruz Lagunas, C. Nouzé, M. Patlán, C.E. Ormsby Jenkins, G. Reyes Terán
Instituto Nacional de Enfermedades Respiratorias, Center for Research in Infectious Diseases, Mexico DF, Mexico

Background: Dysfunction of viral-specific CD8+ T-cells is an important feature of HIV infection. Recent findings have shown
that the coinhibitory molecule PD-1 partly mediates this defect. PD-1 expression on CD8+ T-cells is associated with diminished
proliferation and cytokine secretion, and higher apoptosis sensitivity. However, little has been reported on the impact of PD-1
expression on the cytotoxic function of CD8+ T-cells, one of their most important functions. We measured perforin expression
as an indicator of cytotoxic function on PD-1+CD8+ T-cells in different groups of HIV infected patients.
Methods: Cryopreserved PBMC were obtained from HIV+ controllers (CT; VL<10,000 copies/ml and CD4+ T-cells>500
cells/µl), HIV+ typical progressors (TP; VL>10,000 copies/ml and CD4+ T-cells <500 cell/µl), and HIV- healthy controls (HC).
We used flow cytometry to analyze PD-1 and perforin expression in CD8+ T-cells left unstimulated or after 12h stimulation with
Staphylococcus aureus enterotoxin B (SEB), or a pool of 15-mer peptides spanning the Gag protein.
Results: A lower percentage of perforin+CD8+ T-cells was found in TP when compared to CT (either in unstimulated p=0.006;
SEB p=0.017 or Gag-stimulated cells p=0.017), while the percentage of PD-1+CD8+ T-cells was higher in TP but the difference
did not reach statistical significance. More detailed analyses showed that in Gag-stimulated cells from TP, PD-1+ and PD-1-
CD8+ T-cells did not differ in their ability to express perforin. However, perforin expression in CT was lower in PD-1+CD8+ T-
cells when compared to PD-1-CD8+ T-cells (p=0.043).
Conclusions: Our data suggest that PD-1 functions as a marker of cytotoxic deficiency in HIV-specific CD8+ T-cells in HIV
controllers, but not in individuals with a more advanced immunodeficiency. Further experiments are ongoing to elucidate the
importance of PD-1 as a marker of cytotoxic dysfunction in different stages of the infection.

Country(ies) of Research: Mexico
Presenter: Ms. PhD Maria Candela Iglesias Chiesa, Instituto Nacional de Enfermedades Respiratorias, Mexico DF
Prizes/Awards: IAS Young Investigator Award
Previously presented: V Congreso Nacional de Virología, Mexico, Oct 2007
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